Cardiovascular Immunology Research Core (Core B)

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Heart failure progression is a complex biological process that is precipitated by the maladaptive myocardial response to injury, compounded by failure of the adult heart to replace lost or damaged cardiomyocytes. Conceivably, identifying common pathways that regulate these two seemingly unrelated processes would profoundly impact therapeutic strategies to prevent, and even reverse heart failure progression. Numerous observations by members of the proposed consortium and others support the notion that the endogenous capacity of the neonatal mammalian heart to proliferate fades in the early postnatal life as a switch from hyperplastic to hypertrophic growth of cardiomyocytes takes place. Members of the proposed consortium and others have also previously demonstrated that mechanisms linked to activation of innate immune response may play a role in cardiomyocyte hypertrophy, death and even stimulation of new cardiomyocyte generation. However, whether mechanisms involved in cardiomyocyte cell cycle arrest also play a role in the maladaptive cardiomyocyte response to injury is not known. Indeed, critical components of the inflammatory response appear to underlie both cardiac rejuvenation after injury through positive effects on healing, as well as stimulating cardiomyocytes to proliferate. Therefore, the current proposal brings together 5 groups with expertise in myocardial remodeling, regeneration and immunology with the overall goal of determining the role of immune response signaling in regulation of cardiac growth and regeneration. The 4 Project Leaders are cardiovascular biologist, and thus having a strong immunology presence in the network is paramount for its success, not only to provide technical expertise and reagents, but also to play a crucial consultancy role. Core B will be led by Dr. James Chen, a renowned immunologist, who will play the critical role of providing technical and logistic support to Project Leaders in all matters pertaining to immunological studies. This is a critical and innovative design of the current Program Project as it will allow the 4 Project leaders to seamlessly integrate complex immunological assays and concepts into their research program. As such, Core B will provide a number of essential support services including isolation and characterization of immune cells, performing gene expression analysis studies, providing critical reagents for immunological assays and providing consultation on study design and interpretation. The immunology goal will serve an invaluable role within the network that will enhance synergy, and maximize productivity of all Network Projects